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Postprandial insulin profiles with implantable pump therapy may explain decreased frequency of severe hypoglycemia, compared with intensive subcutaneous regimens, in insulin-dependent diabetes mellitus patients - 11/09/11

Doi : 10.1016/S0002-9343(97)89516-2 
David M. Nathan, MD a, b, , Frederick L. Dunn, MD d, John Bruch, MD d, Charles McKitrick, RN a, Mary Larkin, RN a, Coral Haggan, RN a, Jodi Lavin-Tompkins, RN, ANP d, Dennis Norman, PhD a, c, David Rogers, MD a, Deborah Simon, BA a
a From the Diabetes Research Center, Diabetes Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 
b From the Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 
c From the Department of Psychology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA 
d From the Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA 

*Requests for reprints should be addressed to David M. Nathan, MD, Diabetes Unit, Massachusetts General Hospital, Boston, Massachusetts 02114.

Abstract

Purpose

To examine the mechanism of the decreased frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous intensive therapy.

Patients and methods

Eight subjects with insulin-dependent diabetes mellitus (IDDM), enrolled in an implantable insulin pump study, were admitted to the General Clinical Research Center and on 2 separate days were given either a dose of preprandial insulin chosen to maintain normoglycemia for a standard (450 kcal, 50% carbohydrate) breakfast or 1.75 times the dose. The two doses were administered subcutaneously (by syringe or with an external pump) during one inpatient admission and by implantable pump (intraperitoneally, n = 6; or intravenously, n = 2) during a separate admission. Blood glucose, plasma-free insulin, and neurocognitive function were measured for 4 hours after the meal.

Results

Subcutaneous administration resulted in 7 episodes of hypoglycemia (2 with the usual dose and 5 with the 1.75-fold dose), defined as blood glucose less than 50 mg/dL; implantable pump treatment resulted in only 2 episodes, both with the 1.75-fold dose (P <0.05, Fisher's twotailed test for implantable versus subcutaneous). Compared with subcutaneous delivery, implantable pump therapy provided significantly lower insulin levels during the final 2 hours after administration of the usual dose and the 1.75-fold dose (P <0.005). In addition to the decreased frequency of hypoglycemia, implantable pump therapy resulted in significantly lower area under the glycemia curve during the first 120 minutes with the 1.75-fold dose compared with subcutaneous administration.

Conclusions

The lower frequency of severe hypoglycemia with intensive therapy administered by implantable pump therapy is explained by the more rapid clearance of insulin delivered intraperitoneally or intravenously compared with intensive subcutaneous injection regimens. The lower frequency of severe hypoglycemia with implantable pump therapy compared with subcutaneous therapy demonstrated in clinical trials is confirmed by this study, in which we attempted to induce hypoglycemia.

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** Supported by a research grant from Infusaid, Inc., and through the General Clinical Research Center Program of the National Center of Research Resources, National Institutes of Health (Massachusetts General Hospital RR-01066, Duke University M01-RR-30).


© 1996  Publicado por Elsevier Masson SAS.
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Vol 100 - N° 4

P. 412-417 - avril 1996 Regresar al número
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